Psoriasis (Auckland, N.Z.)最新文献

{"title":"Codon-Usage Bias and Genomic Architecture of 79 Psoriasis-Susceptibility Genes: Implications for Expression Efficiency and Therapeutic Targeting.","authors":"Shanshan Jiang, Lu Chen, Jianghui Li, Fei Gao, Xiaoning Yan, Yiding Zhao","doi":"10.2147/PTT.S545695","DOIUrl":"10.2147/PTT.S545695","url":null,"abstract":"<p><strong>Introduction: </strong>Psoriasis is a chronic autoimmune skin disorder with a complex genetic basis. However, the codon usage patterns and nucleotide features of psoriasis-related genes remain unexplored, despite their potential to influence gene expression and disease progression.</p><p><strong>Methods: </strong>We analyzed 79 psoriasis-associated genes to investigate codon usage bias (CUB) and nucleotide composition. Metrics included GC content, effective number of codons (ENC), and relative synonymous codon usage (RSCU). Evolutionary influences were assessed using correspondence analysis, parity rule 2 (PR2) plots, and neutrality plots.</p><p><strong>Results: </strong>Functional enrichment analysis identified pathway involvement. Comparative genomic analysis evaluated differences in coding sequence and UTR lengths and GC content relative to the genome-wide background. Psoriasis-related genes showed high GC content (mean = 53.3 ± 9.3%) with a strong preference for GC-ending codons, especially at the third codon position (GC3 = 60.6 ± 16.1%). RSCU analysis revealed frequent use of GCC (alanine), CTG (leucine), and GTG (valine). While the mean ENC (46.2 ± 9.9) suggested moderate codon bias, several genes displayed strong bias (ENC < 30). Selection pressure accounted for 71% of codon usage variation, with mutation pressure contributing 29%. Functional enrichment showed significant involvement in IL-17 (FDR = 3.4×10^-3), JAK-STAT (FDR = 3.4×10^-3), and TNF (FDR = 8.0×10^-³) signaling pathways. These genes also tended to have shorter coding sequences and 5'UTRs and higher GC content compared to genome-wide averages.</p><p><strong>Conclusion: </strong>In conclusion, this study reveals that psoriasis-related genes are under strong selective pressure, enriched in key inflammatory pathways, and exhibit codon and nucleotide features that may optimize expression in inflamed tissues. These insights have translational relevance for designing codon-optimized mRNAs, gene therapies, and diagnostic tools tailored to autoimmune diseases like psoriasis.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"479-499"},"PeriodicalIF":5.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vunakizumab for Treatment of Acrodermatitis Continua of Hallopeau: A Case Report and Literature Review.","authors":"Yi Yao, Yingming Ma, Huajie Zhong, Feiying Guo, Jiling Zhu, Yuan Wu, Shunli Tang","doi":"10.2147/PTT.S552600","DOIUrl":"10.2147/PTT.S552600","url":null,"abstract":"<p><p>Acrodermatitis continua of Hallopeau (ACH) is a rare pustular psoriasis subtype, characterized by recurrent sterile pustules on digits, progressive nail deformation and atrophy. ACH is often refractory to different therapeutic modalities, presenting challenges in clinical practice. Emerging evidence indicates that elevated IL-17 levels modulate keratinocyte proliferation and immune cell infiltration, contributing to ACH pathogenesis and representing a promising therapeutic target. Herein, we presented a case of ACH successfully treated with vunakizumab, China's first self-developed anti-IL-17A monoclonal antibody, and reviewed publications reporting IL-17 targeted therapies for ACH, highlighting the potential benefit of IL-17 targeted therapy in ACH management.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"471-478"},"PeriodicalIF":5.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Real-World Effectiveness and Drug Survival of Guselkumab in Patients with Psoriasis: A 5-Year Retrospective Study.","authors":"Edoardo Mortato, Marina Talamonti, Lorenzo Marcelli, Matteo Megna, Annunziata Raimondo, Giacomo Caldarola, Nicoletta Bernardini, Anna Balato, Anna Campanati, Maria Esposito, Claudio Bonifati, Viviana Lora, Luca Potestio, Serena Lembo, Francesco Loconsole, Eleonora De Luca, Nevena Skroza, Dario Buononato, Tommaso Bianchelli, Maria Concetta Fargnoli, Nello Tommasino, Caterina Foti, Clara De Simone, Luca Bianchi, Marco Galluzzo","doi":"10.2147/PTT.S533005","DOIUrl":"10.2147/PTT.S533005","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials have demonstrated the efficacy of guselkumab in psoriasis, however, limited data are available from real-life studies evaluating the long-term effectiveness and drug survival (DS) of guselkumab.</p><p><strong>Objective: </strong>This multicenter study assessed the 5-year efficacy, DS, and predictors of treatment response in a large cohort of patients with psoriasis.</p><p><strong>Methods: </strong>In this retrospective, longitudinal study, we analyzed data from 1024 patients with moderate-to-severe psoriasis treated with guselkumab between 2019 and 2024. PASI scores were evaluated at baseline, 6 months, and 1-5 years. DS (ie, duration of continuous treatment with guselkumab without discontinuation) was assessed using Kaplan-Meier analysis, and logistic regression analysis was used to identify predictors of PASI response.</p><p><strong>Results: </strong>Mean PASI decreased from 14.3±8.8 at baseline to 1.3±2.4 at 6 months, with sustained improvement from 12-60 months (PASI values ranging from 1.0±2.2 to 1.3±3.5). Bioexperienced (ie having previous biological treatment) patients and obese individuals had lower PASI response. Subgroup analyses revealed significantly lower PASI response rates in obese patients, those previously treated with biologics, and those switched from anti-IL-17 agents (p<0.05).Multivariate logistic regression analysis revealed that previous biologic exposure and obesity remained significant negative predictors of achieving PASI 75, PASI 90, and PASI 100 across different time points. Cardiovascular disease emerged as a negative predictor for PASI 90 at 3 months (OR 0.64, 95% CI: 0.42-0.97, p=0.035). The probability of remaining on treatment at 12, 24, 36, 48, and 60 months were 95.85%, 91.73%, 89.74%, 87.08%, and 85.76% respectively. Female sex, ≥3 prior biologics, longer disease duration, and previous anti-IL-17 therapy increased the risk of treatment discontinuation. No significant differences in drug discontinuation were noted between patients with or without comorbidities.</p><p><strong>Conclusion: </strong>This real-world study demonstrates the sustained long-term efficacy and DS of guselkumab in patients with psoriasis. Prior biologic exposure, obesity, and patient history are important factors to consider when initiating treatment for long-term management.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"455-469"},"PeriodicalIF":5.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of Hypertension in Psoriasis: An Analysis of Trends from 2006 to 2023.","authors":"Miao Zhang, Jia-Le Chen, Si-Wei Fan, Xiao-Ying Sun, Ya-Qiong Zhou, Ying Luo, Jiao Wang, Chun-Xiao Wang, Nai-Xuan Lin, Liu Liu, Xin Li","doi":"10.2147/PTT.S532112","DOIUrl":"10.2147/PTT.S532112","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis and hypertension (HTN) are known to be closely related. However, at present, no study has systematically examined the epidemiology of this disease pattern on a global scale.</p><p><strong>Methods: </strong>We examined six databases from their inception until November 1, 2023 and used the Agency for Healthcare Research and Quality and the Newcastle-Ottawa Scale to assess the quality of observational studies. Data analysis was conducted in R. Meta-regression, sensitivity, and subgroup analyses were used to evaluate interstudy heterogeneity. Egger's test and funnel plots were used to evaluate publication bias.</p><p><strong>Results: </strong>We reviewed 200 studies involving 15,010,888 patients. The overall prevalence of HTN among the patients with psoriasis was 32.22%. Overall, South America had the highest prevalence of hypertension among adult patients with psoriasis (52.36%), the three countries with the highest prevalence were Serbia, Singapore and Brazil. The prevalence of mild and severe psoriasis comorbid with HTN was 31.71% [95% CI: 24.40-40.05%] and 33.19% [95% CI: 27.17-39.81%], respectively. The prevalence of HTN in psoriasis vulgaris was 29.71% [95% CI: 25.10-35.15%], while that in psoriatic arthritis was 34.54% [95% CI: 31.27-38.14%].</p><p><strong>Conclusion: </strong>Patients with psoriatic arthritis are more predisposed to requiring hypertension risk screening than patients with psoriasis vulgaris. More population-based prospective observational studies are required to elucidate the mechanisms underlying the coexistence of hypertension in patients with psoriasis.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"443-453"},"PeriodicalIF":5.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning-Driven Prediction Models for Brodalumab Therapeutic Effect and Response Speed in Plaque Psoriasis.","authors":"Lu Peng, Liyang Wang, Ling Chen, Zhu Shen","doi":"10.2147/PTT.S531925","DOIUrl":"10.2147/PTT.S531925","url":null,"abstract":"<p><strong>Purpose: </strong>Biologic therapies have transformed plaque psoriasis treatment, but patient responses remain variable, neces+sitating machine prediction model for personalized therapy.</p><p><strong>Patients and methods: </strong>Transcriptomic and clinical data from moderate-to-severe psoriatic patient biopsies were sourced from GSE117468. Differential gene analysis identified Brodalumab treatment-associated genes. Lasso regression selected response-related genes, and LightGBM was used to build machine learning models. Model robustness was assessed using five-fold cross-validation.</p><p><strong>Results: </strong>Biopsies (n=491) from 116 patients' lesional (LS) and non-lesional (NL) tissues were analyzed, divided into Brodalumab (140 mg or 210 mg) and placebo groups. Responders were defined as achieving ≥75% improvement in Psoriasis Area and Severity Index at week 12. Lasso identified genes from classical psoriasis pathways (IL-17, PPAR signaling, HLA-D alleles) and novel targets (WIF1, SLC44A5, LOC441528, SAA1). Six LightGBM models were trained to predict 12-week treatment response and 4-week response speed using LS, NL, and combined (LS_&_NL) data. LS_&_NL models showed superior performance, achieving AUC-ROC values of 95.14% (140 mg) and 92.83% (210 mg) for 12-week response prediction and 98.70% (140 mg) and 97.51% (210 mg) for 4-week response speed prediction.</p><p><strong>Conclusion: </strong>These models provide robust tools for predicting Brodalumab response, supporting precision medicine and optimizing resource allocation in plaque psoriasis management.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"429-442"},"PeriodicalIF":5.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosimilars for the Treatment of Moderate to Severe Chronic Plaque Psoriasis.","authors":"Paolo Gisondi, Francesco Bellinato, Tea Curic, Giampiero Girolomoni","doi":"10.2147/PTT.S510156","DOIUrl":"10.2147/PTT.S510156","url":null,"abstract":"<p><p>Psoriasis is an immune-mediated chronic inflammatory skin disease affecting over 60 million adults and children worldwide and can occur at any age, from childhood to adulthood. If the patient has a diffuse form of psoriasis, affecting more than ten percent of the body surface, or involving sensitive areas such as the face, scalp, nails, and/or palmoplantar region, he or she is a candidate for systemic therapy. Currently, several drugs are approved for the treatment of moderate to severe chronic plaque psoriasis in Europe and US. These are classified into conventional systemics, biologics, and small molecules. These immunomodulatory agents are available in different forms of administration, such as oral, subcutaneous, and intravenous. Novel treatments, including biologics and small molecules, can provide reliable disease control with a good safety profile even in the long term and have greatly improved the quality of life for many patients. Nevertheless, biologics can be expensive, placing a significant burden on national healthcare systems and creating a barrier to access for patients in need of these life-changing therapies. A biosimilar drug is a biologic medical product that is highly similar to an already approved reference biologic drug (also known as the originator). Biosimilars have no clinically meaningful differences in terms of safety, purity, and efficacy compared to the reference product. Biosimilar drugs have been on the market-and therefore in clinical practice-for several years now, helping to overcome these challenges. Biosimilars have the potential to improve access to biologic therapies for psoriasis while reducing healthcare costs. The aim of this narrative review is to describe biosimilars and the potential cost-saving benefits their use can offer. In this review, we will discuss adalimumab, infliximab, etanercept, and ustekinumab, as well as their corresponding biosimilars.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"401-410"},"PeriodicalIF":5.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Skin-Brain Axis in Psoriasis and Depression: Roles of Inflammation, Hormones, Neuroendocrine Pathways, Neuropeptides, and the Microbiome.","authors":"Lipeng Tang, Huichang Bi, Kangguang Lin, Yisi Chen, Haiyan Xian, Yuan Li, Hesong Xie, Guangjuan Zheng, Peng Wang, Yonggen Chen, Biying Yang, Yaqian Tan, Qi Song, Maojie Wang, Guanzhuo Li, Jiameng Chang, Yuanjun Guan, Kwok-Fai So, Chuanjian Lu","doi":"10.2147/PTT.S535900","DOIUrl":"10.2147/PTT.S535900","url":null,"abstract":"<p><p>Psoriasis, a common chronic inflammatory skin disease affecting approximately 2-3% of the global population, frequently co-occurs with depression. This highly prevalent comorbidity significantly impairs patients' quality of life. Despite the substantial physical and mental health burden imposed by psoriatic depression, the underlying pathophysiological mechanisms connecting psoriasis and depression remain poorly understood. In this review, we explored several pathological processes that may contribute to psoriasis-associated depression, including immune cells dysregulations, hormones imbalances, hypothalamic-pituitary-adrenal (HPA) axis dysfunctions, neuropeptides expression abnormalities, and gut dysbiosis. The primary purpose of this review was to present a comprehensive overview of the pathogenic mechanisms linking psoriasis and depression. These insights may guide trans-disciplinary interventions aimed at both skin and mood symptoms.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"411-428"},"PeriodicalIF":5.2,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Effect of Plasma Fatty Acid Profiles on Psoriasis Risk: Genetic Evidence from a Mendelian Randomization Study.","authors":"Lei Yao, Xi Wang, Dongmei Lu, Suyan Tian","doi":"10.2147/PTT.S538518","DOIUrl":"10.2147/PTT.S538518","url":null,"abstract":"<p><strong>Introduction: </strong>Emerging evidence indicates that omega-3 fatty acids from fish oil may serve as beneficial dietary supplements for psoriasis management. Clinical observations demonstrate a significant association between psoriasis improvement and increased docosahexaenoic acid (DHA) levels. However, the causal relationship between fatty acids and psoriasis risk requires further investigation.</p><p><strong>Methods: </strong>Using summary-level genome-wide association study (GWAS) data, we applied univariable (UVMR), reverse, and multivariable (MVMR) Mendelian randomization analyses to assess causal effects of multiple fatty acids-including polyunsaturated (PUFA), saturated (SFA), monounsaturated (MUFA), omega-3/6 fatty acids, DHA, eicosapentaenoate (EPA) and docosapentaenoate (DPA)-on psoriasis risk.</p><p><strong>Results: </strong>The analysis revealed that higher circulating levels of omega-3 fatty acids were significantly associated with a reduced risk of psoriasis development (UVMR: OR = 0.900, p = 0.022; MVMR: OR = 0.862, p = 0.007). Sensitivity analyses supported the robustness of this causal relationship, with consistent effects across multiple MR methods. Notably, DHA (UVMR: OR = 0.788, p = 0.006; MVMR: OR = 0.856, p = 0.021) drove this inverse association, while EPA and DPA showed marginal contributions.</p><p><strong>Conclusion: </strong>This study provides valuable insights for targeted nutritional strategies to prevent and manage psoriasis, but further validation is needed.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"389-399"},"PeriodicalIF":5.2,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Skin Clearance: Personalized Strategies for DLQI Improvement in Psoriasis -Insights From a Shanghai Prospective Cohort.","authors":"Xin Ma, Quanruo Xu, Le Kuai, Fanlingzi Shen, Zhen Duan, Xiangjin Gao, Rui Zhang, Ruiping Wang","doi":"10.2147/PTT.S534881","DOIUrl":"10.2147/PTT.S534881","url":null,"abstract":"<p><strong>Introduction: </strong>Psoriasis is a chronic immune-mediated disease that significantly impacts patients clinically and psychologically. Physician-assessed severity measures, including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Physician Global Assessment (PGA), often fail to capture patient-reported outcomes, particularly when clinical improvement and perceived quality-of-life gains are misaligned.</p><p><strong>Purpose: </strong>To clarify the association between clinical improvements and Dermatology Life Quality Index (DLQI) outcomes, identify predictors of substantial DLQI improvement (≥90% reduction), and explore reasons for suboptimal DLQI responses in patients achieving skin clearance.</p><p><strong>Methods: </strong>In this 12-week prospective study, 551 psoriasis patients were enrolled at Shanghai Skin Diseases Hospital. Data on demographics, clinical severity (PASI, BSA, and PGA), DLQI scores, and treatment modalities were collected. Logistic regression analyses were employed to assess the dose-response relationships between improvements in clinical parameters and DLQI reduction, and to identify factors of suboptimal DLQI improvement among patients achieving significant skin clearance.</p><p><strong>Results: </strong>Median DLQI improved significantly (8.0 to 3.0) at week 12, with 24.1% of patients achieving ≥90% DLQI reduction. Strong dose-response associations existed between clinical severity improvements (PASI, BSA, PGA) and DLQI gains. PASI₇₅ responders were significantly more likely to achieve substantial DLQI improvement (OR = 2.48, 95% CI: 1.51-4.07). However, only 33.3% of PASI₇₅ achievers reached ≥90% DLQI improvement. Early clinical response (as early as week 4) strongly predicted superior DLQI outcomes. Female sex, older age, lower baseline DLQI scores, and shorter disease duration were associated with achieving high skin clearance but suboptimal DLQI improvement.</p><p><strong>Conclusion: </strong>Early clinical response effectively predicts substantial DLQI improvement, whereas demographic and disease-related factors help identify patients at risk for suboptimal quality-of-life gains despite significant skin clearance. These insights support personalized therapeutic strategies aimed at improving patient satisfaction beyond skin clearance alone.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"373-387"},"PeriodicalIF":5.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TYK2 rs34536443 (P1104A) Variant Suppresses ICAM1-Mediated Inflammation: Insights From Mendelian Randomization and Functional Analyses.","authors":"Bowen Dai, Ye Tang, Bin Zhang, Guangyao Xu, Yanan Zhang, Kan Ze","doi":"10.2147/PTT.S535434","DOIUrl":"10.2147/PTT.S535434","url":null,"abstract":"<p><strong>Background: </strong>Genetic susceptibility to psoriasis involves multiple loci, including TYK2 (Tyrosine Kinase 2), which is associated with various autoimmune diseases. However, its specific role and mechanisms in psoriasis remain unclear. This study aimed to identify psoriasis-associated proteins using Summary-based Mendelian Randomization (SMR) and to explore their regulatory mechanisms.</p><p><strong>Methods: </strong>SMR analysis integrating pQTL data was conducted to identify proteins linked to psoriasis, revealing ICAM1 (Intercellular Adhesion Molecule 1) as a potential pathogenic factor. A key SNP, rs34536443 (P1104A), located in TYK2, was found to regulate ICAM1. To assess its function, THP-1 cells carrying the TYK2-P1104A mutation were generated, and ICAM1 and cytokine expression were analyzed following LPS stimulation. The effect of the TYK2 inhibitor Deucravacitinib was tested in an imiquimod (IMQ)-induced psoriasis mouse model.</p><p><strong>Results: </strong>SMR identified ICAM1 as a causal protein for psoriasis, regulated by the TYK2 SNP rs34536443. In TYK2-P1104A mutant THP-1 cells, LPS-induced ICAM1 expression was significantly reduced, with ICAM5 unaffected. The mutation also suppressed IL-1β, TNF-α, IL-6, and IL-18 expression, suggesting anti-inflammatory effects. Single-cell RNA-seq revealed enrichment of TYK2, ICAM1, and ICAM5 in dendritic cells and monocytes. In vivo, Deucravacitinib significantly downregulated ICAM1 in the IMQ-induced psoriasis model, with minimal effect on ICAM5.</p><p><strong>Conclusion: </strong>This study identifies ICAM1 as a key mediator in psoriasis via SMR analysis and implicates the TYK2 SNP rs34536443 in its regulation. The TYK2-P1104A variant attenuates ICAM1 and cytokine expression, and Deucravacitinib downregulates ICAM1 in vivo. These findings provide mechanistic insights into the TYK2-ICAM1 axis and support the therapeutic potential of TYK2 inhibitors for psoriasis.</p>","PeriodicalId":74589,"journal":{"name":"Psoriasis (Auckland, N.Z.)","volume":"15 ","pages":"361-372"},"PeriodicalIF":5.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}